Trabectedin: A Review of its use in soft tissue sarcoma and ovarian cancer

Drugs

Volumn 70, Issue 3, 2010, Pages 355-376

  Carter, Natalie J ^a   Keam, Susan J ^a  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

Author keywords

Adis Drug Evaluations; General; Ovarian cancer; Research and development; Soft tissue sarcoma; Trabectedin; Treatment

Indexed keywords

CAPECITABINE; CARBOPLATIN; CISPLATIN; CYCLOSPORIN A; CYTOCHROME P450 3A4; CYTOCHROME P450 INHIBITOR; DOCETAXEL; DOXORUBICIN; GEMCITABINE; IFOSFAMIDE; IRINOTECAN; METYRAPONE; PACLITAXEL; PARACETAMOL; PHENANTHRENE; PIPERONYL BUTOXIDE; PROADIFEN; RIFAMPICIN; RITONAVIR; TRABECTEDIN; VERAPAMIL;

ABDOMINAL PAIN; ADVANCED CANCER; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CLINICAL TRIAL; DIARRHEA; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDICATION; DRUG METABOLISM; DRUG TOLERABILITY; DYSPNEA; FATIGUE; HUMAN; IN VITRO STUDY; KIDNEY FAILURE; LEIOMYOSARCOMA; LIPOSARCOMA; LIVER TOXICITY; MONOTHERAPY; MULTIPLE ORGAN FAILURE; NAUSEA; NEUTROPENIA; NONHUMAN; OVARY CANCER; PHARMACODYNAMICS; RECURRENT CANCER; REVIEW; RHABDOMYOLYSIS; SEPSIS; SIDE EFFECT; SOFT TISSUE SARCOMA; THROMBOCYTOPENIA; TREATMENT RESPONSE; VOMITING;

ANTINEOPLASTIC AGENTS, ALKYLATING; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DIOXOLES; FEMALE; HUMANS; NEOPLASM RECURRENCE, LOCAL; OVARIAN NEOPLASMS; SARCOMA; TETRAHYDROISOQUINOLINES;

EID: 77249088752     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: None     Document Type: Review

References (105)

1. Schoffski P Dumez H Wolter P et al. Clinical impact of trabectedin (ecteinascidin-743) in advanced/metastatic soft tissue sarcoma. Expert Opin Pharmacother 2008 Jun; 9(9): 1609-1618.
2. Casali PG, Jost L, Sleijfer S, et al. Soft tissue sarcomas: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008 May; 19 Suppl. 2: ii89-93
3. Hartmann JT, Patel S. Recent developments in salvage chemotherapy for patients with metastatic soft tissue sarcoma. Drugs 2005; 65 (2): 167-178 (Pubitemid 40139381)
4. Clark MA, Fisher C, Judson I, et al. Soft-tissue sarcomas in adults. N Engl J Med 2005 Aug 18; 353: 701-711
5. Cancer Research UK. Statistics and outlook for soft tissue sarcoma [online]. Available from URL: http://www. cancerhelp.org.uk/help/default.asp? page=4569 [Accessed 2010 Jan 20]
6. Fayette J, Coquard IR, Alberti L, et al. ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol 2006; 18 (4): 347-353
7. Carter NJ, Keam SJ. Trabectedin: a review of its use in the management of soft tissue sarcoma and ovarian cancer. Drugs 2007; 67 (15): 2257-2276
8. Barthomeuf C, Bourguet-Kondracki M-L, Kornprobst J-M. Marine metabolites overcoming or circumventing multidrug resistance mediated by ATP-dependent transporters: a new hope for patient with tumors resistant to conventional chemotherapy. Anticancer Agents Med Chem 2008; 8 (8): 886-903
9. Cvetkovic RS, Figgitt DP, Plosker GL. ET-743 [published erratum appears in Drugs 2002; 62 (11): 1634]. Drugs 2002; 62(8): 1185-1192
10. Cuevas C, Francesch A. Development of Yondelis® (tra-bectedin, ET-743): asemisynthetic process solves the supply problem. Nat Prod Rep 2009 Mar; 26 (3): 322-337
11. Simoens C, Korst AE, De Pooter CM, et al. In vitro inter-action between ecteinascidin 743 (ET-743) and radiation, in relation to its cell cycle effects. Br J Cancer 2003 Dec 15; 89 (12): 2305-2311
12. Friedman D, Hu Z, Kolb EA, et al. Ecteinascidin-743 in-hibits activated but not constitutive transcription. Cancer Res 2002 Jun 15; 62 (12): 3377-3381
13. Herrero AB, Martin-Castellanos C, Marco E, et al. Cross-talk between nucleotide excision and homologous recombination DNA repair pathways in the mechanism of action of antitumor trabectedin. Cancer Res 2006; 66 (16): 8155-8162
14. Takebayashi Y, Pourquier P, Zimonjic DB, et al. Anti-proliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat Med 2001 Aug; 7 (8): 961-966
15. Tavecchio M, Simone M, Erba E, et al. Role of homo-logous recombination in trabectedin-induced DNA damage. Eur J Cancer 2008 Mar; 44 (4): 609-618
16. Soares DG, Escargueil AE, Poindessous V, et al. Replica-tion and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743. Proc Natl Acad Sci USA 2007 Aug; 104(32): 13062-13067
17. Casado JA, Rio P, Marco E, et al. Relevance of the Fan-coni anemia pathway in the response of human cells to trabectedin. Mol Cancer Ther 2008 May; 7 (5): 1309-1318
18. Guirouilh-Barbat J, Redon C, Pommier Y. Transcription-coupled DNA double-strand breaks are mediated via the nucleotide excision repair and the Mre11-Rad50-Nbs1 complex. Mol Biol Cell 2008 Sep; 19 (9): 3969-3981
19. Aune GJ, Takagi K, Sordet O, et al. Von Hippel-Lindau-coupled and transcription-coupled nucleotide excision repair-dependent degradation of RNA polymerase II in response to trabectedin. Clin Cancer Res 2008 Oct 15; 14 (20): 6449-6455
20. Forni C, Minuzzo M, Virdis E, et al. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther 2009 Feb; 8 (2): 449-457
21. Li WW, Takahashi N, Jhanwar S, et al. Sensitivity of soft tissue sarcoma cell lines to chemotherapeutic agents: identification of ecteinascidin-743 as a potent cytotoxic agent. Clin Cancer Res 2001 Sep 1; 7 (9): 2908-2911
22. Romero J, Zapata I, Cordoba S, et al. In vitro radio-sensitisation by trabectedin in human cancer cell lines. Eur J Cancer 2008 Aug; 44 (12): 1726-1733
23. Takahashi N, Li WW, Banerjee D, et al. Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells. Clin Cancer Res 2001 Oct 1; 7 (10): 3251-3257
24. D'Incalci M, Colombo T, Ubezio P, et al. The combination of yondelis and cisplatin is synergistic against human tumor xenografts. Eur J Cancer 2003; 39: 1920-1926
25. Riccardi A, Meco D, Ubezio P, et al. Combination of tra-bectedin and irinotecan is highly effective in a human rhabdomyosarcoma xenograft. Anticancer Drugs 2005; 16 (8): 811-815
26. Meco D, Colombo T, Ubezio P, et al. Effective combination of ET-743 and doxorubicin in sarcoma: preclinical studies. Cancer Chemother Pharmacol 2003 Aug; 52 (2): 131-138
27. Gore L, Rivera E, Lavallee K, et al. Phase I combination study of trabectedin (T) and capecitabine (C) in patients with advanced malignancies [abstract no. 2079]. J Clin Oncol 2006 Jun 20; 24 (18 Suppl. 1): 98s
28. Vidal L, Garcia-Martin M, Tan S, et al. Phase I combina-tion study of trabectedin and carboplatin in advanced solid tumours [abstract no. 396P]. Ann Oncol 2004; 15 Suppl. 3: iii106
29. Von Mehren M, Buck D, Temmer E, et al. Phase I study of trabectedin (T) in combination with docetaxel (D) in patients with advanced malignancies [abstract no. 2068]. J Clin Oncol 2006 Jun 20; 24 (18 Suppl. 1): 96s
30. Papadopoulos KP, Chu Q, Patnaik A, et al. Phase I and pharmacokinetics (PK) study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors [abstract no. 2029]. J Clin Oncol 2006 Jun 20; 24 (18 Suppl. 1): 86
31. Sessa C, Perotti A, Noberasco C, et al. Phase I clinical and pharmacokinetic study of trabectedin and doxorubicin in advanced soft tissue sarcoma and breast cancer. Eur J Cancer 2009 May; 45 (7): 1153-1161
32. Blay J-Y, von Mehren M, Samuels BL, et al. Phase I combina-tion study of trabectedin and doxorubicin in patients with soft-tissue sarcoma. Clin Cancer Res 2008 Oct 15; 14 (20): 6656-6662
33. Sessa C, Cresta S, Noberasco C, et al. Phase I clinical and pharmacokinetic study of trabectedin and cisplatin in solid tumours. Eur J Cancer 2009 Aug; 45 (12): 2116-2122
34. Messersmith WA, Jimeno A, Ettinger D, et al. Phase I trial of weekly trabectedin (ET-743) and gemcitabine in patients with advanced solid tumors. Cancer Chemother Pharmacol 2008 Dec; 63 (1): 181-188
35. von Mehren M, Schilder RJ, Cheng JD, et al. A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies. Ann Oncol 2008; 19 (10): 1802-1809
36. Jimeno J, Schoffski P, Casali P, et al. Personalized therapy with trabectedin (Yondelis®) in advanced pre-treated sarcomas [abstract no. 7505]. EJC Supplements 2007 Sep; 5 (4): 403-404
37. HUGO Gene Nomenclature Committee. Approved gene names [online]. Available from URL: http://www.genenames. org/index.html [Accessed 2010 Jan 20]
38. GrossoF, Sanfilippo R, Virdis E, etal. Trabectedin in myxoid liposarcomas (MLS): a long-term analysis of a single-institution series. Ann Oncol 2009 Aug; 20 (8): 1439-1444
39. Gronchi A, Palmerini E, Demetri G, et al. A phase II clinical trial of neoadjuvant trabectedin in patients with non metastic advanced myxoid/round cell liposarcoma (MRCL) [abstract no. 9400]. Eur J Cancer Suppl 2009 Sep; 7 Suppl. 2: 590
40. Grosso F, Jones RL, Demetri GD, et al. Efficacy of tra-bectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 2007 Jul; 8 (7): 595-602
41. Allavena P, Signorelli M, Chieppa M, et al. Anti-inflammatory properties of the novel antitumor agent Yondelis® (trabectedin): inhibition of marcophage differentiation and cytokine production. Cancer Res 2005 Apr 1; 65 (7): 2964-2971
42. Donald S, Verschoyle RD, Greaves P, et al. Complete protection by high-dose dexamethasone against the he-patotoxicity of the novel antitumor drug Yondelis® (ET-743) in the rat. Cancer Res 2003 Sep 15; 63 (18): 5902-5908
43. Lee JK, Leslie EM, Zamek-Gliszczynski MJ, et al. Modulation of trabectedin (ET-743) hepatobiliary disposition by multidrug resistance- associated proteins (Mrps) may prevent hepato-toxicity. Toxicol Appl Pharmacol 2008 Apr 1; 228 (1): 17-23
44. Fetterly GJ, Owen JS, Stuyckens K, et al. Semimechanistic pharmacokinetic/pharmacodynamic model for hepato-protective effect of dexamethasone on transient transa-minitis after trabectedin (ET-743) treatment. Cancer Chemother Pharmacol 2008 Jun; 62 (1): 135-147
45. Pharma Mar SA. Trabectedin (Yondelis®): summary of product characteristics [online]. Available from URL: http:// www.ema.europa.eu/ humandocs/PDFs/EPAR/yondelis/ emea-combined-h773en.pdf [Accessed 2010 Jan 19]
46. Puchalski TA, Ryan DP, Garcia-Carbonero R, et al. Pharmacokinetics of ecteinascidin 743 administered as a 24-h continuous intravenous infusion to adult patients with soft tissue sarcomas: associations with clinical characteristics, pathophysiological variables and toxicity. Cancer Chemother Pharmacol 2002 Oct; 50 (4): 309-319
47. Garcia-Carbonero R, Supko JG, Manola J, et al. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol 2004 Apr 15; 22 (8): 1480-1490
48. del Campo JM, Pardo B, Cervantes A, et al. Pharmacoki-netics of trabectedin in women with recurrent ovarian cancer. EJC Supplements 2007 Sep; 5 (4): 321
49. van Kesteren C, Cvitkovic E, Taamma A, et al. Pharmacoki-netics and pharmacodynamics of the novel marine-derived anticancer agent ecteinascidin 743 in a phase I dose-finding study. Clin Cancer Res 2000 Dec 1; 6 (12): 4725-4732
50. Beumer JH, Rademaker-Lakhai JM, Rosing H, et al. Me-tabolism of trabectedin (ET-743, Yondelis®) in patients with advanced cancer. Cancer Chemother Pharmacol 2007 Jun; 59 (6): 825-837
51. Salazar R, Pardo B, Majem M, et al. Phase I clinical and pharmacological trial of trabectedin (T) in 3 hour infusion every 3 weeks (3h/q3w) in patients with advanced cancer and hepatic function disorder [abstract no. 2080]. J Clin Oncol 2006 Jun 20; 24 (18 Suppl. 1): 99
52. Beumer JH, Lopez-Lazaro L, Schellens JHM, et al. Evaluation of human plasma protein binding of trabectedin (Yondelis®, ET-743). Curr Clin Pharmacol 2009 Jan; 4 (1): 38-42
53. Brandon EFA, Sparidans RW, Guijt K-J, et al. In vitro char-acterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis®, Trabectedin®), a novel marine anti-cancer drug. Invest New Drugs 2006; 24: 3-14
54. Vermeir M, Hemeryck A, Cuyckens F, et al. In vitro studies on the metabolism of trabectedin (Yondelis®) in monkey and man, including human CYP reaction phenotyping. Biochem Pharmacol 2009; 77: 1642-1654
55. Brandon EFA, Meijerman I, Klijn JS, et al. In-vitro cyto-toxicity of ET-743 (trabectedin, Yondelis®), a marine anti-cancer drug, in the Hep G2 cell line: influence of cytochrome P450 and phase II inhibition, and cytochrome P450 induction. Anticancer Drugs 2005; 16: 935-943
56. Beumer JH, Franke NE, Tolboom R, et al. Disposition and toxicity of trabectedin (ET-743) in wild-type and mdr 1 gene (P-gp) knock-out mice. Invest New Drugs. Epub 2009 Feb 24
57. Hing J, Perez-Ruixo JJ, Stuyckens K, et al. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of trabectedin (ET-743, Yondelis®) induced neutropenia. Clin Pharmacol Ther 2008 Jan; 83 (1): 130-143
58. Perez-Ruixo JJ, Zannikos P, Hirankarn S, et al. Population pharmacokinetic meta-analysis of trabectedin (ET-743, Yondelis®) in cancer patients. Clin Pharmacokinet 2007; 46 (10): 867-884
59. Demetri GD, Chawla SP, von Mehren M, et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol 2009 Sep; 27 (25): 4188-4196 Plus supplementary material available from URL: http://jco.ascopubs.org/ cgi/content/full/27/25/4188 [Accessed 2010 Jan 20]
60. Chawla S, Blay JY, Schuetze S, et al. Efficacy of second-line trabectedin in patients with advanced liposarcomas and leiomyosarcomas progressing despite prior conventional chemotherapy [abstract no. 9427]. Eur J Cancer Suppl 2009 Sep; 7 Suppl. 2: 598
61. Sanfilippo R, Grosso F, Virdis E, et al. Rechallenge with trabectedin in patients with responding myxoid liposarcoma [abstract no. 10575]. 45th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29-Jun 2; Orlando (FL)
62. Yovine A, Riofrio M, Blay JY, et al. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol 2004 Mar 1; 22 (5): 890-899
63. Le Cesne A, Blay JY, Judson I, et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol 2005 Jan 20; 23 (3): 576-584
64. Demetri G, Blay JY, Yovine A, et al. Efficacy and safety of trabectedin in soft tissue sarcoma (STS) are independent of patient age [abstract no. 9402]. Eur J Cancer Suppl 2009 Sep; 7 Suppl. 2: 590
65. Le Cesne A, Gianni L, Maki R, et al. Translocation-related sarcomas (TRS): a retrospective analysis of activity with trabectedin [abstract no. 9401]. Eur J Cancer Suppl 2009 Sep; 7 Suppl. 2: 590
66. Johnson & Johnson Pharmaceutical Research Development L.L.C. A study of the safety and effectiveness of trabectedin for the treatment of localized myxoid/round liposarcoma [ClinicalTrials.gov identifier NCT00579501]. US National Institutes of Health ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Jan 20]
67. Johnson & Johnson Pharmaceutical Research & Develop-ment L.L.C. A study to provide access to trabectedin in patients with soft tissue sarcoma who have persistent or recurrent disease and who are not expected to benefit from currently available standard of care treatment [Clinical-Trials.gov identifier NCT00210665]. US National Institutes of Health ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Jan 20]
68. Johnson & Johnson Pharmaceutical Research & Develop-ment L.L.C. A study of the safety and effectiveness of trabectedin versus doxorubicin-based chemotherapy in patients with translocation-related sarcomas (TRS) [Clin-icalTrials.gov identifier NCT00796120]. US National Institutes of Health ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Jan 20]
69. Lau L, Supko JG, Blaney S, et al. A phase I and pharma-cokinetic study of ecteinascidin-743 (Yondelis®) in children with refractory solid tumors: a Children's Oncology Group study. Clin Cancer Res 2005 Jan 15; 11 (2): 672-677 (Pubitemid 40116894)
70. National Cancer Institute (NCI). Ecteinascidin 743 in treating young patients with recurrent or refractory soft tissue sarcoma or Ewing's family of tumors. [Clinical-Trials.gov identifier NCT00070109]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials. gov [Accessed 2010 Jan 20]
71. Monk BJ, Herzog TJ, Kaye S, et al. Trabectedin plus pe-gylated liposomal doxorubicin in recurrent ovarian cancer. J Clin Oncol In press
72. European Medicines Agency. Assessment report for Yondelis® (EMEA/640507/2009) [online]. Available from URL: http://www.ema.europa.eu/ humandocs/PDFs/EPAR/ yondelis/EMEA-H-773-II-08-AR.pdf [Accessed 2010 Jan 19]
73. Del Campo JM, Roszak A, Bidzinski M, et al. Phase II ran-domized study of trabectedin given as two different every 3 weeks dose schedules (1.5mg/m2 24-hour or 1.3mg/m2 3-hour) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Ann Oncol 2009 Nov; 20 (11): 1794-1802
74. Krasner CN, McMeekin DS, Chan S, et al. A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer 2007 Dec 17; 97 (12): 1618-1624
75. Sessa C, De Braud F, Perotti A, et al. Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails. J Clin Oncol 2005 Mar 20; 23 (9): 1867-1874
76. Bidzinski M, Poveda A, Vermorken J, et al. Influence of an independent review on PFS and response assessments in a phase III clinical trial in relapsed ovarian cancer [abstract no. 8064]. Eur J Cancer Suppl 2009 Sep; 7 Suppl. 2: 468
77. Herzog TJ, Vermorken JB, Pujade-Lauraine E, et al. Cor-relation of CA-125 and RECIST evaluation in recurrent ovarian cancer (ROC): results from a randomized phase III study of trabectedin (T) with pegylated liposomal doxorubicin (PLD) versus PLD alone. 45th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29-Jun 2; Orlando (FL)
78. Poveda A, Kaye SB, McCormack RT, et al. Circulating tumor cells (CTC) in a study of relapsed/recurrent advanced ovarian cancer: an exploratory analysis in the ova-301 phase 3 study of pegylated liposomal doxorubicin (PLD) compared with trabectedin and PLD [abstract no. 5551]. 45th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29-Jun 2; Orlando (FL)
79. Poveda A, KayeS, Herzog T, et al. Correlation of RNA expres-sion of DNA repair genes with clinical outcomes of advanced ovarian cancer (OC) pts treated with pegylated liposomal doxorubicin (PLD) vs trabectedin + PLD in the ET743-OVA-301 clinical trial [abstract no. 8005]. Eur J Cancer Suppl 2009 Sep; 7 Suppl. 2: 451-452
80. Krasner CN, Poveda A, Herzog T, et al. Health-related quality of life/patient-reported outcomes in relapsed ovarian cancer: results from a randomized phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone [abstract no. 5526]. 45th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29-Jun 2; Orlando (FL)
81. McMeekin S, del Campo JM, Colombo N, et al. Tra-bectedin (T) in relapsed advanced ovarian cancer (ROC): a pooled analysis of three phase II studies [abstract no. 5579]. J Clin Oncol 2007 Jun 20; 25 (18 Suppl. 1): 293s.
82. Plus oral presentation and poster presented at the 43rd Annual Meeting of the American Society of Clinical Oncology; 2007 Jun 1-5; Chicago (IL)
83. Ludwig J, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005 Nov; 5 (11): 845-856
84. Demetri GD, Schuetze S, Blay J-Y, et al. Long-term results of a randomized phase II study of trabectedin by two different dose and schedule regimens in patients with advanced liposarcoma or leiomyosarcoma after failure of prior an-thracyclines and ifosfamide [abstract no. 10509 plus oral presentation]. 45th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29-Jun 2; Orlando (FL)
85. Vergote I, Vermorken J, Pujade-Lauraine E, et al. Safety analysis of trabectedin in combination with pegylated liposomal doxorubicin (PLD) vs PLD alone in ovarian cancer patients 65 years of age and older [abstract no. 8028]. Eur J Cancer Suppl 2009 Sep; 7 Suppl. 2: 458
86. Grosso F, Dileo P, Sanfilippo R, et al. Steroid premedica-tion markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma. Eur J Cancer 2006 Jul; 42 (10): 1484-1490
87. Ortho Biotech Products. Doxil (doxorubicin HCl liposome injection) for intravenous infusion: US prescribing information [online]. Available from URL: http://www.access data.fda.gov/drugsatfda-docs/label/2008/050718s033lbl.pdf [Accessed 2010 Jan 20]
88. SP Europe. Caelyx 2mg/mL concentrate for solution for infusion: EU prescribing information [online]. Available from URL: http://www.emea.europa.eu/ humandocs/PDFs/ EPAR/Caelyx/H-089-PI-en.pdf [Accessed 2010 Jan 20]
89. Pharmamar. Yondelis® has been approved for the treatment of ovarian cancer and soft tissue sarcoma by the Philippines [online]. Available from URL: http://translate.google.co. nz/translate?hl=en&sl=es&u=http://www. pharmamar.com/ &ei=onVaSqPpLYXQtAOb0tmDCw&sa=X&oi=translate &resnum=1&ct=result&prev=/search%3Fq%3DPharma mar%26hl%3Den [Accessed 2010 Jan 20]
90. Nielsen OS, Blay J-Y, Judson IR, et al. Metastatic soft tissue sarcoma in adults: prognosis and treatment options. Am J Cancer 2003; 2 (3): 211-221
91. Kopp H-G, Patel S, Brucher B, et al. Potential combina-tion chemotherapy approaches for advanced adult-type soft-tissue sarcoma. Am J Clin Dermatol 2008; 9 (4): 207-217
92. Wagner A. Treatment of advanced soft tissue sarcoma: conventional agents and promising new drugs. JNCCN 2007Apr; 5 (4): 401-410
93. Garcia-Carbonero R, Supko JG, Maki RG, et al. Ectei-nascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol 2005 Aug 20; 23 (24): 5484-5492
94. Van Glabbeke M, Verweij J, Judson I, et al. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer 2002 Mar; 38 (4): 543-549
95. von Mehren M. Trabectedin: a targeted chemotherapy? [letter]. Lancet Oncol 2007 Jul; 8 (7): 565-567
96. Nijhuis P, Schaapveld M, Otter R, et al. Epidemiological aspects of soft tissue sarcomas (STS): consequences for the design of clinical STS trials. Eur J Cancer 1999; 35 (12): 1705-1710
97. Cooper N, Quinn MJ, Rachet B, et al. Survival from cancer of the ovary in England and Wales up to 2001. Br J Cancer 2008 Sep 23; 99 Suppl. 1: S70-2
98. Aebi S, Castiglione M. Epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008; 19 Suppl. 2: ii4-16
99. Aletti GD, Gallenberg MM, Cliby WA, et al. Current management strategies for ovarian cancer. Mayo Clin Proc 2007 Jun; 82 (6): 751-770
100. Bhoola S, Hoskins WJ. Diagnosis and management of epithelial ovarian cancer. Obstet Gynecol 2006 Jun; 107 (6): 1399-1410
101. Cancer Research UK. Ovarian cancer survival statistics [online]. Available from URL: http://info.cancerresearchuk. org/cancerstats/types/ovary/ survival/ [Accessed 2010 Jan 20]
102. Morgan RJ, Alvarez RD, Armstrong DK, et al. Clinical practice guidelines in oncology: ovarian cancer. J Nat Comp Canc Netw 2008 Sep; 6 (8): 766-794
103. Medscape Medical News. Trabectedin for ovarian cancer rejected by FDA committee [online]. Available from URL: http://www.medscape.com/viewarticle/ 706350 [Accessed 2010 Jan 20]
104. Medical News Today. FDA issues complete response letter for trabectedin combined with Doxil® [online]. Available from URL: http://www. medicalnewstoday.com/articles/ 163619.php [Accessed 2010 Jan 20]
105. Pharmamar. Yondelis® [online]. Available from URL: http:// translate.google.co.nz/translate?hl=en&sl=es&u=http:// www.pharmamar.com/&ei=33IfSvWBBJ78tgPKurCZBA &sa=X&oi= translate&resnum=1&ct=result&prev=/search %3Fq%3Dpharmamar%26hl%3Den [Accessed 2009 Jul 8]